Autor(es): McFarlane, Melanie; Arias-Goeta, Camilo; Martin, Estelle; O'Hara, Zoe; Lulla, Aleksei; Mousson, Laurence; Rainey, Stephanie M.; Misbah, Suzana; Schnettler, Esther; Donald, Claire L.; Merits, Andres; Kohl, Alain; Failloux, Anna-Bella

Resumo: Replication of arboviruses in their arthropod vectors is controlled by innate immune responses. The RNA sequence-specific break down mechanism, RNA interference (RNAi), has been shown to be an important innate antiviral response in mosquitoes. In addition, immune signaling pathways have been reported to mediate arbovirus infections in mosquitoes; namely the JAK/STAT, immune deficiency (IMD) and Toll pathways. Very little is known about these pathways in response to chikungunya virus (CHIKV) infection, a mosquito-borne alphavirus (Togaviridae) transmitted by aedine species to humans resulting in a febrile and arthralgic disease. In this study, the contribution of several innate immune responses to control CHIKV replication was investigated. In vitro experiments identified the RNAi pathway as a key antiviral pathway. CHIKV was shown to repress the activity of the Toll signaling pathway in vitro but neither JAK/STAT, IMD nor Toll pathways were found to mediate antiviral activities. In vivo data further confirmed our in vitro identification of the vital role of RNAi in antiviral defence. Taken together these results indicate a complex interaction between CHIKV replication and mosquito innate immune responses and demonstrate similarities as well as differences in the control of alphaviruses and other arboviruses by mosquito immune pathways. Chikungunya virus (CHIKV) is a mosquito-borne human-pathogenic arbovirus of the Togaviridae family, genus Alphavirus. Arbovirus replication in vectors, such as mosquitoes, is not passively tolerated but leads to immune responses, that control virus infection. These responses therefore represent interesting targets for novel intervention strategies. Mosquito antiviral immune responses, such as small RNA pathways or immune signaling pathways, are increasingly well studied but it is not known which one mediate antiviral effects against CHIKV in particular. Here we screened four key immune responses in vitro for their antiviral potential against CHIKV and only the exogenous RNA interference was found to mediate antiviral activity. This was confirmed in vivo in Aedes aegypti mosquitoes. Immune signaling pathways were not found to mediate antiviral activity but were inhibited by CHIKV. This shows interesting differences and similarities to other mosquito-borne alphaviruses that increase our understanding of alphavirus-mosquito interactions.

Palavras-Chave: Antiviral agents; Replication; Pest control; Aquatic insects; Disease transmission; Public health; Vectors; RNA-mediated interference; Immune response; Infection; Antiviral activity; Signal transduction; Aedes aegypti; Chikungunya virus

Imprenta: Plos Neglected Tropical Diseases, v. 8, n. 7, 2014.

Descritores: Aedes aegypti - Biochemistry ; Aedes aegypti - Immune response ; Aedes aegypti - RNA ; Aedes aegypti - Virus ; Aedes aegypti - Transmission ; Aedes aegypti - Immunology ; Aedes aegypti - Public health

Data de publicação: 2014

INDICADORES

ACESSO